Capecitabine and Radiation Therapy With or Without Panitumumab in Treating Patients With Advanced Rectal Cancer

Swiss Group for Clinical Cancer Research

Status and phase: Completed; Phase 2

Conditions: Colorectal Cancer

Treatments: Radiation: 3-dimensional conformal radiation therapy; Drug: capecitabine; Biological: panitumumab; Procedure: therapeutic conventional surgery

Study type: Interventional

Funder types: Other

Identifiers

NCT00814619

CDR0000629101

SWS-SAKK-41-07

SAKK 41/07

EU-20894

EudraCT-2008-006012-38

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy that uses a 3-dimensional (3-D) image of the tumor to help focus thin beams of radiation directly on the tumor, and giving radiation therapy in higher doses over a shorter period of time, may kill more tumor cells and have fewer side effects. Monoclonal antibodies, such as panitumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving capecitabine together with 3-D conformal radiation therapy is more effective with or without panitumumab in treating patients with advanced rectal cancer.

PURPOSE: This randomized phase II trial is studying giving capecitabine together with radiation therapy to see how well it works with or without panitumumab in treating patients with advanced rectal cancer.

Full description

OBJECTIVES:

• To assess the efficacy and safety of neoadjuvant capecitabine and concurrent 3-dimensional conformal radiotherapy with vs without panitumumab in patients with advanced K-ras unmutated rectal cancer.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, T stage (T3 vs T4), tumor localization measured from caudal part of the tumor to the anocutaneous line (< 10 cm vs ≥ 10 cm), and number of EGFR gene copies (< 2.9 vs ≥ 2.9). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive panitumumab IV over 30-90 minutes on days 1, 15, 29, 43, and 57 and oral capecitabine twice daily on days 8-40. Beginning on day 8, patients undergo daily fractions of 3-D conformal radiotherapy 5 days a week for 5 weeks. Beginning approximately 6 weeks after completion of panitumumab and chemoradiotherapy, patients undergo surgery.
• Arm II: Patients receive oral capecitabine twice daily on days 1-33. Patients undergo concurrent 3-D conformal radiotherapy 5 days a week for 5 weeks. Beginning 6 weeks after completion of chemoradiotherapy, patients undergo surgery.

After completion of study therapy, patients are followed periodically for up to 3 years.

Enrollment: 68 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced adenocarcinoma of the rectum with or without nodal involvement

  • Stage mrT3-4 and/or mrN1-2, M0
  • Tumors must express wild type K-ras gene

• No distant metastasis

PATIENT CHARACTERISTICS:

• WHO performance status 0-1
• Able to undergo surgery
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 100 g/L
• Creatinine clearance ≥ 50 mL/min
• AST ≤ 2.5 times upper limit normal (ULN)
• Total bilirubin ≤ 1.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must agree to use effective contraception during and for 12 months after completion of study
• No malignancy within the past 5 years with the exception of adequately treated cervical carcinoma in situ or localized nonmelanoma skin cancer
• No psychiatric disorder that would preclude understanding study-related information, giving informed consent, or complying with oral drug intake
• No prior existing conditions that would preclude radiotherapy
• No clinically significant (i.e., active) cardiac disease (e.g., congestive heart failure, symptomatic coronary artery disease, and cardiac arrhythmia even if controlled with medication) or myocardial infarction within the past 12 months
• No lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
• No serious underlying medical condition that, in the judgement of the investigator, could impair the ability of the patient to participate in the trial (e.g., active autoimmune disease or uncontrolled diabetes)
• No known dihydropyrimidine dehydrogenase deficiency
• No known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs

PRIOR CONCURRENT THERAPY:

• More than 30 days since prior treatment in a clinical trial
• No other concurrent experimental drugs, anticancer therapy, or investigational treatments
• No prior treatment for rectal cancer
• No prior anti-EGFR antibody therapy (e.g., cetuximab) or small-molecule EGFR inhibitors (e.g., erlotinib hydrochloride)
• No concurrent treatment with brivudine, lamivudine, ribavirin, or any other nucleoside analogues
• No organ allografts
• No concurrent drugs contraindicated for use with the trial drugs
• No other concurrent anti-EGFR-targeting agents
• No other concurrent radiotherapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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68 participants in 2 patient groups

Arm I

Experimental group

Description:

Patients receive panitumumab IV over 30-90 minutes on days 1, 15, 29, 43, and 57 and oral capecitabine twice daily on days 8-40. Beginning on day 8, patients undergo daily fractions of 3-D conformal radiotherapy 5 days a week for 5 weeks. Beginning approximately 6 weeks after completion of panitumumab and chemoradiotherapy, patients undergo surgery.

Treatment:

Radiation: 3-dimensional conformal radiation therapy

Biological: panitumumab

Drug: capecitabine

Procedure: therapeutic conventional surgery

Arm II

Active Comparator group

Description:

Patients receive oral capecitabine twice daily on days 1-33. Patients undergo concurrent 3-D conformal radiotherapy 5 days a week for 5 weeks. Beginning 6 weeks after completion of chemoradiotherapy, patients undergo surgery.

Treatment:

Radiation: 3-dimensional conformal radiation therapy

Drug: capecitabine

Procedure: therapeutic conventional surgery